Abstracts (complete list) - Wissenschaft Online

Arthur Liesz, Elisabeth Suri-Payer, Claudia Veltkamp, Henrike Dörr, Clemens Sommer,
Thomas Giese, Roland Veltkamp
Regulatory T Cells (Treg) are Important Cerebroprotective
Immunomodulators in Acute Experimental Stroke by an
Interleukin-10 Dependent Pathway.
Inflammatory cascades contribute substantially to secondary infarct growth after
ischemic brain damage. Because CD4+CD25+Foxp3+ Treg are important negative
immunomodulators in various inflammatory diseases, we studied the role of Treg in
experimental stroke and the involved immunosuppressive mechanisms.
Permanent focal cerebral ischemia was induced by middle cerebral artery occlusion
(MCAO) in C57BL/6 mice and Treg were eliminated in one group of mice by preischemic
anti-CD25 mAb injection. While no difference was detectable between groups at 24h,
infarct volumes became significantly larger between 3-7d after MCAO in Treg depleted
mice. Correspondingly, transfer of only CD4+CD25- T cells into RAG-/- mice resulted in
larger infarcts than transfer of total CD4+ cells. Treg started to invade the brain 3d
after MCAO (shown by FACS and immunohistology). The lack of Treg resulted in
significantly higher microglial activation (Iba1+ cells) 24h after MCAO. Further, levels of
proinflammatory cytokines (RT-PCR and ELISA) were significantly more elevated in the
ischemic brain hemisphere and the serum of Treg depleted mice at various time points
after MCAO compared to control mice. The intraventricular injection of IL-10 prevented
the secondary infarct growth in Treg depleted mice. Finally, RAG-/- mice receiving
wildtype CD4+CD25- T cells plus Treg with impaired IL-10 secretion had significantly
larger infarcts than mice receiving additional wildtype Treg.
In conclusion, we show that Treg are physiological master anti-inflammatory modulators
in ischemic stroke which substantially reduce secondary infarct progression. This effect
is mainly mediated by early IL-10 signalling, inhibition of microglial activation and
cytokine expression as well as delayed Treg invasion.